Polymicrogyria is a human brain malformation disorder in which cerebral cortex organization is perturbed, causing the formation of too many gyri. Mutations in GPR56, a G protein-coupled receptor of unknown function, cause polymicrogyria of the frontal and parietal lobes. Gpr56 is expressed in cortical progenitors, which give rise to several cell-types of the mature neocortex, suggesting that Gpr56 regulates cortical progenitors. To test this hypothesis, Gpr56 will be misexpressed in embryonic neocortex by in utero electroporation of wild-type and mutated Gpr56 alleles and Gpr56 siRNA constructs, and electroporated cortex will be analyzed for changes in cortical progenitor cells. Furthermore, the identification of Gpr56 indicates a novel signaling pathway required for proper neocortex development. To determine how Gpr56 exerts is signaling effects, Gpr56 binding partners will be identified and tested for their ability to activate Gpr56. These experiments will contribute to a stronger understanding of neocortex development and the causes of congenital neurological disease.]